title: Combination chemotherapy with cyclophosphamide and ftorafur against advanced L1210 murine leukemia.
abstract: The antitumor activity of cyclophosphamide (CP) in combination with ftorafur (FT) against advanced L1210 murine leukemia was investigated and compared with the activity of the combination of CP and 5-FU. CP at doses of 200--350 mg/kg was highly active, the most effective dose (% treated/control = 327) being 300 mg/kg. The activity of FT up to the LD10 dose and of 5-FU at 50 mg/kg was minimal (% treated/control less than or equal to 142). Coadministration of 200 mg/kg of FT with 100 mg/kg of CP resulted in an increase in activity as compared with the respective dose of CP alone as did the coadministration of 400 mg/kg of FT with 200 mg/kg of CP; the activities, however, were no better than that resulting from treatment with 300 mg/kg of CP alone. The coadministration of CP and 600 mg/kg of FT resulted in an increase in host toxic reactions and loss of antitumor activity, as did the coadministration of 400 mg/kg of FT with 300 mg/kg of CP. Treatment with FT at 400 or 600 mg/kg 24 hours before or after administration of CP at 200 or 300 mg/kg did not increase the activity over that occurring when the respective combinations of the drugs were coadministered. The activity of the combination of CP with 5-FU at doses previously reported to be synergistic was equal to that observed when mice were treated with 300 mg/kg of CP alone. These data suggest that FT increases the cytotoxicity of CP but that the combination is not synergistic.
mesh_terms: D000818:Animals; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D007939:Leukemia L1210 / Q000188:drug therapy*; D008297:Male; D051379:Mice; D005641:Tegafur / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D005641:Tegafur; D003520:Cyclophosphamide; D005472:Fluorouracil